During 1915 and 1917 a number of papers were published by Dr. Walter Jacobs and coworkers at the Rockefeller Institute for Medical Research describing the general bactericidal character of quaternary ammonium salts of hexamethylenetetramine. The bactericidal activity of these compounds was primarily attributed to the presence of the hexamethylenetetramine nucleus; however, the degree or extent of this activity was said to be determined by the nature of the molecular groups adducted with the hexamethylenetetramine. The principal mode of action of these quaternary ammonium salts of hexamethylenetetramine was said to be the controlled, regulated decomposition of the hexamethylenetetramine nucleus to liberate formaldehyde. The following group of papers by Jacobs and coworkers are of interest in this regard: Proc. Nat. Acad. Sci. U.S.A., 1, 226 (1915); J. Biol. Chem., 20, 659 (1915); J. Biol. Chem., 21, 465 (1915); J. Exp. Med., 24, 563 (1916); and J. Exp. Med., 25, 363 (1917). These Jacobs papers, however, do not describe any quaternary ammonium adducts of hexamethylenetetramine with unsaturated acyclic dihalides.
In U.S. Pat. No. 3,228,829 Wolf and a coworker at the Dow Chemical Company have more recently described as antimicrobial agents a group of one-to-one quaternary ammonium adducts of hexamethylenetetramine with unsaturated halides and dihalides. Among the useful unsaturated halides and dihalides described are the dihaloalkenes and haloalkynes, specifically 1,3-dichloropropene.
In French Pat. No. 1,363,240 Frank and coworkers at Farbenfabriken Bayer even more recently described as antibacterial agents a group of one-to-one quaternary ammonium adducts of hexamethylenetetramine with .alpha.,.omega.-dihalogenated hydrocarbons. Among the group of useful .alpha.,.omega.-dihalogenated hydrocarbons described is 1,4-dichlorobutene-2.
We have now discovered that a two-to-one quaternary ammonium adduct can unexpectedly be prepared by reacting hexamethylenetetramine with 3,4-dichlorobutene-1. Moreover, this two-to-one quaternary ammonium adduct is more active and less toxic than the one-to-one adducts described by both Wolf and Frank and consequently is significantly more advantageous as an antimicrobial agent, particularly from a safety and environmental standpoint.